The proposed experiments are designed to investigate the relationship of the structure of factor IX to its biological function. To accomplish this aim, the reactions of purified normal factor IX will be compared to reactions of abnormal genetic variants of factor IX isolated from hemophilia B patients and to normal factor IX that is chemically modified by different techniques. The reactions to be compared will include: activation by factor XIa, kallikrein and Russell's Viper Venom, calcium binding, phospholipid binding; and interaction with purified factor VII, factor X, calcium and phospholipid. In addition, primary structure, and immunochemistry of both normal and abnormal factor IX forms will be studied. For a better understanding of the role of factor IX in blood coagulation, human factor IX and IXa will be compared to bovine and canine counterparts.